Foglino R, Barbetti F, Morotti E, Castorani V, Rigamonti A, Frontino G, Barera G, Bonfanti R
Pediatric Diabetes Unit IRCCS Ospedale San Raffaele, Vita Salute San Raffaele University, Milan, Italy.
Monogenic Diabetes Clinic, Unit of Endocrinology and Diabetes, Bambino Gesù Children Hospital IRCCS, Rome, Italy.
Front Genet. 2024 Jun 24;15:1414451. doi: 10.3389/fgene.2024.1414451. eCollection 2024.
Rabson-Mendenhall syndrome (RMS), a rare disorder characterized by severe insulin resistance due to biallelic loss-of-function variants of the insulin receptor gene (INSR), presents therapeutic challenges (OMIM: 262190). This case study explores the efficacy of adjunctive therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in the management of RMS in an 11-year-old male patient with compound heterozygous pathogenic variants of INSR. Despite initial efforts to regulate glycemia with insulin therapy followed by metformin treatment, achieving stable glycemic control presented a critical challenge, characterized by persistent hyperinsulinism and variable fluctuations in glucose levels. Upon the addition of empagliflozin to metformin, improvements in glycated hemoglobin (HbA1c) and time in range (TIR) were observed over a 10-month period. After 10 months of treatment, empagliflozin therapy led to a clinically meaningful reduction in HbA1c levels, decreasing from 8.5% to 7.1%, along with an improvement in TIR from 47% to 74%. Furthermore, regular monitoring effectively averted normoglycemic ketoacidosis, a rare complication associated with SGLT2 inhibitor therapy. This case highlights the potential of SGLT2i as adjunctive therapy in RMS management, particularly in stabilizing glycemic variability. However, further research is warranted to elucidate the long-term efficacy and safety of this therapeutic approach in RMS and similar insulin resistance syndromes.
拉布森 - 门登霍尔综合征（RMS）是一种罕见的疾病，其特征是由于胰岛素受体基因（INSR）的双等位基因功能丧失变异导致严重的胰岛素抵抗，这带来了治疗挑战（OMIM：262190）。本病例研究探讨了钠 - 葡萄糖协同转运蛋白2抑制剂（SGLT2i）辅助治疗在一名患有INSR复合杂合致病变异的11岁男性RMS患者管理中的疗效。尽管最初尝试通过胰岛素治疗然后使用二甲双胍治疗来调节血糖，但实现稳定的血糖控制面临着关键挑战，其特征是持续的高胰岛素血症和血糖水平的波动。在二甲双胍中加入恩格列净后，在10个月的时间里观察到糖化血红蛋白（HbA1c）和血糖达标时间（TIR）有所改善。经过10个月的治疗，恩格列净治疗使HbA1c水平有了具有临床意义的降低，从8.5%降至7.1%，同时TIR从47%提高到74%。此外，定期监测有效地避免了正常血糖性酮症酸中毒，这是一种与SGLT2抑制剂治疗相关的罕见并发症。本病例突出了SGLT2i作为RMS管理辅助治疗的潜力，特别是在稳定血糖变异性方面。然而，有必要进一步研究以阐明这种治疗方法在RMS和类似胰岛素抵抗综合征中的长期疗效和安全性。
